Lipid, lipoproteins and atherogenesis profiles in sickle cell disease among Central African patients

Lipid and lipopproteins disorders are well established in sera from sickle cell disease (SCD) patients out of Central Africa. The present case-control study was conducted to compare serum levels of total cholesterol (TC), HDL-C, triglycerides (TG), LDL-C and TC/HDL-C ratio (atherogenic index) from SCD homozygotes (SS) in steady state, SCD heterozygotes (AS) and controls (AA) in Brazzaville, Congo. Significant reductions of TC and LDL-C vs. increase in TG were reported in SS. However, significant decrease in HDL-C and increase in atherogenic index were observed in AS. We recommend prevention of oxidative stress, dyslipidemia and atherosclerosis in SCD using hygiene-diet measures. Only longitudinal studies in large populations will provide pathophysiological basis of lipid and lipoproteins disorders in SCD.     

The sickle gene: a marker for blood pressure?

Blood pressure patterns were studied in 224 Nigerians comprising 22 families with at least one child with sickle cell anemia (SS) and 18 families without sickle cell anemia (AA) in a community with a high frequency of the sickle trait (AS). Among the offspring (n = 162; mean age: 10.1 years), systolic blood pressure did not differ between the SS, AS, or AA groups. However, the SS group had significantly lower diastolic blood pressure than the AS or AA groups (60.6 versus 66.5 and 65.4 mm Hg, respectively; P < .01). After controlling for genotype, age, body mass index, and sex, regression analysis revealed that age was the only independent correlate of blood pressure.     

Study of haemoglobin S percentage and haematological parameters in sickle cell trait

A total of 101 individuals who showed AS pattern on haemoglobin electrophoresis were included in this study and various haematological investigations were carried out on them. Of these, 79 cases were grouped as AS patients. Twenty two healthy relatives of sickle anemia patients were grouped as AS controls. Twenty AA controls were also included in this study. Haemoglobin S (HbS) and hemoglobin A (HbA) quantitation was carried out. The frequency distribution of HbS percentage showed that maximum subjects had HbS levels above 33%. A female predominance was seen in subjects of sickle cell trait. Haemoglobin levels and total red cell counts of AS patients were found to be significantly lower than those of AS controls. Reticulocyte counts and hematocrit values of AS patients were found to be significantly higher than AS controls. MCV and MCH values of AS patients were found to be significantly lower, but MCHC was not significantly altered.     

Red cell distribution width in sickle cell disease

Red cell distribution width (RDW), an electronically determined index of anisocytosis, was examined in 60 patients with sickle cell anemia (Hb SS), 28 patients with hemoglobin sickle cell (SC) disease, and seven patients with sickle cell-beta(+) thalassemia (S-thal). All patients were adults and in the steady state of their disease. The RDW was greater in sickle cell patients than in 39 healthy, age and race matched controls without hemoglobinopathy (Hb AA). Patients with sickle cell anemia had higher mean RDW than those with Hb SC disease or with S-thal. The mean RDWs in the latter two disorders were not significantly different. In SS patients, the RDW correlated significantly with the degree of anemia and reticulocytosis. A group of 18 SS patients was studied while in acute painful crisis. Their mean RDW was not different from that in the steady state. Mean WBC and red cell volume, however, were significantly higher during pain crisis.     

Chromatographic measurements of hemoglobin A2 in blood samples that contain sickle hemoglobin

In the sickle cell syndromes, Hb A2 measurements aid in the differential diagnosis of sickle cell anemia from sickle-beta-thalassemia. The purpose of this study is to assess the Hb A2 levels in samples containing sickle hemoglobin (Hb S) by the use of an automated high performance liquid chromatography system (HPLC-Variant beta-thalassemia Short Program). The blood samples analyzed were from individuals of African descent living in the state of Tennessee who had either sickle cell trait (Hb AS), sickle cell disease (Hb SS), or sickle cell-hemoglobin C disease (Hb SC). Interestingly, the Hb A2 levels determined by HPLC were found elevated in samples containing Hb S. The Hb A2 mean in Hb AS samples (n=146) is 4.09% (SD +/- 0.42, range 2.20 to 5.20%); in Hb SS samples (n=33) it is 3.90% (SD +/- 1.08, range 0.60 to 5.90%); and in Hb SC samples (n=27) it is 4.46% (SD +/- 0.70, range 2.30 to 5.91%). The Hb A2 mean by HPLC in normal individuals (Hb AA, n=70) is 2.57% (SD +/- 0.25, range 2.1 to 3.0%), and the Hb A2 range in beta-thalassemia carriers is 4 to 9%. Our results show that the Hb A2 levels in Hb S-containing samples partially overlap with those expected from beta-thalassemia carriers. The hemoglobinopathy laboratory should be aware of this apparent elevation in Hb A2 levels determined by HPLC in individuals carrying Hb S. Other factors, such as family history and clinical symptoms, should be taken into account before a diagnosis of sickle cell trait, sickle-beta-thalassemia, or sickle cell anemia is made.     

Benign sickle cell disease in Saudi Arabia: survival estimate and population dynamics

A survey of 8,084 adult Saudi male employment applicants yielded 872 with the sickle cell trait (AS) and 51 with sickle cell disease. Based on the known distribution of hemoglobin S genes between oasis and non-oasis populations in Saudi Arabia, and on calculation of the expected number of abnormal homozygotes within the non-oasis and oasis subgroups as well as the entire employment applicant group, it appears that virtually 100% of Saudis with SS disease survive to adult life. Saudi Arabs and other Caucasian populations in the Middle East exhibit a benign type of SS disease as compared with Blacks in Africa and the Americas. In the Middle East, gene contributions from SS individuals will shift equilibrium frequencies to higher levels than encountered in Black populations under sustained selective pressures, and the polymorphism will tend to be stable with decline in selective pressure. There are some indications that the hemoglobin S gene may have been a recent import into the Middle East.     

Renal pathology in hemizygous sickle cell mice

Transgenic mice have been developed that express exclusively human sickle cell beta hemoglobin and have major pathological features found in humans with sickle cell disease. These mice provide a unique opportunity to investigate the fundamental mechanisms of this disease and to design new strategies to correct the associated genetic defect(s). We found that in breeding males expressing only adult human alpha-globin and sickle beta-globin (homozygous SS mice) with females containing these transgenes plus one copy of the mouse beta-globin gene (hemizygous SS mice) greater than expected numbers of hemizygous offspring were produced than homozygous mice (carrying no mouse beta-globin gene). These hemizygous mice, expressing the human alpha and sickle beta(s) transgenes in combination with mouse beta+/-, were used for our preliminary studies of their renal pathology. No kidney lesions were found in the control (129/Sv) mice, whereas about 50% of the hemizygous SS mice showed mild-to-severe kidney lesions, including glomerulonephritis, cystic atypical hyperplastic tubules, and general nephropathy. Kidneys of some hemizygous mice were normal or showed minimal nephropathy, yet those of the susceptible phenotype developed a mild-to-more-severe form of renal lesions. The tubular epithelium of kidneys of hemizygous mice of the more affected phenotype exhibited increased expression of inducible nitric oxide synthase with an increased 3-nitrotyrosine in close proximity. There was also a stronger immunostaining for vascular cell adhesion molecule-1 in the interstitial capillary cells as well as the tubular epithelial cells of the renal cortex, compared with normal control mice. The occurrence of a high incidence of renal abnormalities in our hemizygous SS mice suggests that these mice may provide a suitable model to study the pathogenesis of nephropathy resulting from altered blood flow and/or insufficient oxygen delivery.     

The Placenta: A Diagnostic Tool in Sickle Cell Disorders

Examination of the placenta for the presence of sickling is an accurate, simple, inexpensive, and readily available technique for determining the presence of sickle cell disorders. There were 24 placental specimens out of 904 which showed evidence of sickling. The importance of this confirming procedure can be seen in the uncovering of two cases of false negative reports from conventional testing.     

Hemolysis in sickle cell disease as measured by endogenous carbon monoxide production. A preliminary report

To detect and quantitate temporal variations of the hemolytic rate in sickle cell disease, the authors measured endogenous carbon monoxide (CO) production in five normal subjects, nine patients with sickle cell anemia (SS) in steady clinical state, and two patients with sickle cell-hemoglobin C (SC) disease in and out of pain crises. The red blood cell life span calculated from these data (RCLSco) ranged from 81.2 to 102.9 days (mean +/- standard deviation [SD] 88.0 +/- 9.2, coefficient of variation [CV] 10.2%) for the normal subjects and 8.0-24.7 days (mean +/- SD 12.1 +/- 5.1, CV 42.1%) for those with SS. Although the individual figures for RCLSco for the normal subjects and those with SS fell within the range previously obtained by radioisotopic techniques for the respective groups, the mean values calculated from the CO technique were slightly (though not significantly) shorter for the normal subjects and about 25% shorter for the subjects with SS (P less than 0.01). Repetitive studies were performed in four subjects with SS who were clinically stable; the temporal variability in the calculated hemolytic rate differed considerably from patient to patient (CV 3.6%, 7.0%, 17.0%, 28.0%). In two patients concurrent RCLS studies were performed by the CO technique and 51Cr tagged red blood cells. In one patient, the RCLS was similar by the two techniques, in the other, a two exponent 51Cr curve did not permit calculation of RCLS. In the two patients with SC disease there was no difference in RCLSco during and after recovery from pain crisis. Although the CO technique may overestimate the turnover of circulating heme mass, especially in the presence of hemolysis, the results of serial studies in a small number of patients with SS suggest but do not prove temporal variations in hemolytic rate in SS.     

Serum amylase levels in homozygous sickle cell patients.

Serum amylase was evaluated in a group of 26 steady-state homozygous sickle cell (SS) patients and 11 age-matched HbAA controls. Half (50%) of the SS patients had values above normal while only two of the control group had slightly elevated values. The SS patients had a mean +/- SD value of 301.46 +/- 119.40 iu/L while the control group had 274.36 +/- 89.70 iu/L. The difference between these two values is statistically significant (P less than .05). Males in both groups had significantly higher mean serum amylase values. The values in the SS group did not show an association with age. Higher levels in SS patients suggest a predisposition to chronic pancreatitis.     

Influence of fetal haemoglobin rate (FHb) on the oxidizing stress in homozygote sickle cell patient living in Abidjan, Côte-d'Ivoire

Sickle cell anemia being involved in oxidizing stress, our objective was to study the influence of the fetal haemoglobin rate (FHb) on the lipoperoxidation markers in homozygote sickle cell patient in tropical African surroundings. The study population was composed of 73 subjects among whom 57 homozygote sickle cell subjects and 16 healthy control cases. These subjects were distributed in 4 groups according to FHb rate: group 1 (FHb rate under 10%), group 2 (FHb rate ranging from 10 and 20%), group 3 (FHb rate above 20%), group 4 (control cases with no sickle cell disease). On the biological level, the markers of plasma lipoperoxidation represented by substances reacting with thiobarbituric acid (TBARS) significantly increased in sickle cell patients comparatively to control cases (p = 10(-6)). A strong positive correlation (r = +0,70, p<0,01) was found between HbS and the TBARS rate. Comparison of biological parameters of homozygote sickle cell patients according to HbF rate shows that TBARS rate is all the more low as the HbF rate is high (p = 0,02). Moreover the number of irreversible and reversible sickle cells is higher in the group 1 which has the highest rate of TBARS. This observation is confirmed by a coefficient of positive correlation between TBARS and reversible sickle cells (r = +0,40, p < 0,01). This study strengthens the role played by HbF on the modulation of physiopathology of homozygote sickle cell anemia by the control, among others, of free radicals.     

Sickle cell anemia patient with sarcoidosis-associated inguinal lymph node and lung infiltration

Sarcoidosis is a chronic, systemic inflammatory disease of unknown etiology, characterized by noncaseating granulomatous infiltration of any organ. Sickle cell anemia (SCA) is the homozygoid form of sickle cell disease (SCD), which includes a group of genetic disorders characterized by production of an abnormal hemoglobin S (HbS). There are a few case reports with coexistence of sarcoidosis and SCA. We reported a 47-year-old female with SCA and sarcoidosis.     

Sickle cell anemia: does myocardial ischemia occur during crisis?

The possibility that myocardial ischemia may be associated with chest pain during painful crises was evaluated prospectively in 20 patients (11 women and nine men) with sickle cell disease (19 SS, 1 S beta + thalassemia). Sixteen of 20 (80%) had abnormal ECGs, 7 (35%) had transient ST-T wave changes, and 3 (15%) had persistent ST-T wave changes, both consistent with ischemia; 6 (30%) had nonspecific ST-T changes, and 4 (20%) had normal tracings. Serum enzymes (CK, SGOT, LDH) were abnormal in 16 of 19 (84%); 1 had CK-MB detected, (5%) and 1 had LDH1 to LDH2 reversal. All 10 Tc-99m pyrophosphate scans performed were negative; 4 of 6 (66%) thallium-201 scans had focal defects, and 5 of 8 (63%) radionuclide angiograms (MUGAs) had focal wall motion abnormalities. Three of 8 (38%) MUGAs showed cardiac dilation, diffuse hypokinesis, and reduced ejection fractions. Thus, myocardial damage may be a potentially serious complication of patients with sickle cell anemia who present with chest pain during painful crises. Studies are indicated to define the significance and pathophysiology of these observations.     

Assessment of the use of transfusion therapy and complications in orthopedic surgery in patients with sickle-cell anemia: retrospective study]

Red blood cells (RBCs) transfusion is a common practice in the treatment or for the prevention of complications of patients with sickle-cell disease. In surgery, pre-operative transfusions are frequently given to prevent peri-operative complications. There is no consensus however on the best regimen of transfusion for this purpose. The transfusion techniques are muliple. In addition, pre-operative transfusion therapy is reported to be largely responsible for an increased morbidity and mortality in patients with sickle cell anemia undergoing surgery. During the period 1990-2000, 16 patients (4 men and 12 women) with a mean age of 37 years and various major sickle cell hemoglobinopathies underwent 32 total hip arthroplasty for femoral head necrosis. Nine patients with sickle-cell trait were included as control group. Twelve of them had haemoglobin SS (HbSS), 2/16 had HbSC, 2/16 had HbS/betathalassemia. Operative transfusion were given in only 12/32 procedures, 4 were performed pre-operatively and 8 intra-operatively. Simple transfusion (mean: 2.5 packed red cells) were administered in all the procedures. The main complications observed in our patients were anemia by hemolysis and haemorrhagic shock, vaso-occlusive crisis and chest syndrome. Anemia requiring transfusions was significatively related to the procedures with pre-operative transfusion. In the light of our result, we would like to propose transfusional protocol--if needed--only intra-operatively.     

Pathology of the Glomerulus in Sickle Cell Anemia With and Without Nephrotic Syndrome

Glomeruli from 6 cases of sickle cell disease (SS) with the nephrotic syndrome (NS) were compared histologically and quantitatively with glomeruli from 9 cases of SS, 10 cases of sickle cell trait (SCT), 4 cases of other hemoglobinopathies, all without NS, and normal controls. Five of 6 patients with SS and NS had extensive reduplication of their glomerular basement membranes and mild mesangial proliferation. Similar but milder lesions occurred in SS without NS but not in SCT or controls. Incidental renal disease occurred in 1 patient with SS and NS. Nephrotic syndrome was probably secondary to effects of sickle cell disease. Glomeruli in SS were significantly larger (>70%) than in SCT and controls. Mean total glomerular area per unit area of cortex in SS with normal BUN significantly exceeded that of SCT, which, in turn, was significantly greater than that of controls. Mechanisms for the histologic lesions and hypertrophy of the glomeruli were suggested.     

Viral seroprevalence, transfusion and alloimmunization in adults with sickle cell anemia in Guadeloupe]

We retrospectively studied the prevalence of anti HIV 1 and 2, anti-HTLV-I, anti-Hepatitis B and C viruses (HBV and HCV) antibodies, anti-HBV vaccinal coverage, transfused patients and alloimmunizations frequencies among adult sickle cell patients attending the sickle cell center (SCC) of Guadeloupe. The data were collected from the medical files of the centre. Among the studied samples (n = 331) no transfusional HIV contamination was observed. All patients with HTLV-I (n = 11, 3.3% of whole sample) and anti-HCV (n = 9, 2.7%) positive serology had transfusion history. Five patients (1.5%) had an active hepatitis B. Vaccination against HBV efficiently protected 247 patients (74.4%) and 57 had post-hepatitis B antibodies. We observed that 213 patients (64%) had a history of transfusion (88% of SS patients and 36% of the SC patients, p < 0.05). Fifty-four patients (16%) presented alloimmunization, 4 of them have never been transfused. These results show that it is still necessary to optimise transfusion protocol and their safety, and to diagnose viral contamination in transfused sickle cell patients.     

子痫前期患者胎盘组织中visfatin蛋白与mRNA表达及意义

目的:探讨内脂素(visfatin,VF)在子痫前期(PE)患者胎盘组织中的表达及意义。方法:选择2011年8月至2013年12月在温州医科大学附属第一医院住院分娩的孕妇共计100例,根据病情轻重分为重度PE组、轻度PE组和正常妊娠组。采用苏木素-伊红染色法观察3组胎盘组织病理变化;免疫组化法及real-time PCR技术分别检测3组胎盘VF蛋白及mRNA的表达并分析其与子痫前期发病的关系。结果:PE的病理改变主要表现为细胞滋养细胞及合体滋养细胞结构紊乱且形态不完整;细胞滋养细胞增生,合体滋养细胞结节增多;绒毛毛细血管减少、淤血。免疫组化及real-time PCR结果显示胎盘组织中内脂素定位于合体及细胞滋养层细胞的胞浆,随着病情的加重,VF蛋白及mRNA表达量逐渐升高,重度PE组明显高于正常妊娠组,差异有统计学意义(P0.05)。结论:PE患者存在绒毛血管内皮细胞损伤和功能紊乱。胎盘VF蛋白及mRNA在PE孕妇中高表达,表明VF与PE的发生具有一定关系。     

Severity in phenotypic expression of homozygous sickle cell disease (Hb.SS) – Does hypermelanotic or hypomelanotic skin status of affected patients play a role?

Abnormal hemoglobin distribution on global map, of which hemoglobin S (Hb.S) accounted for about 80% of the disorders resulting from them are more prevalent in the tropics and sub-tropics. Homozygous sickle cell disease (Hb.SS) is the most common and most severe form of sickle cell disease (SCD) in phenotypic expression. The prevalence and severity in phenotypic expression of SCD had been noted to decrease farther away from the equatorial region, with prevalence rate of sickle cell trait of about 2% and less than 1% in North African coast and South Africa, respectively, compared to about 10-40% in the equatorial region. Controlling for human migration, the distribution of prevalence and severity of SCD tend to correspond with the degree of pigmentation of skin color on global map with areas of hyperpigmentation having the likelihood of higher prevalence and severity, while areas of hypopigmentation are characterized by the reverse. This distribution had been observed to correspond with skin color variation on global map based on Von Luschan's chromatic scale. Empirical observation had also shown that individual homozygous SCD patients who are lighter in skin color tend to manifest a less severe phenotypic expression of the disease condition when compared to those with darker skin color using the yard stick of frequency in sickle cell crises. The hypothesis is; would hypermelanotic or hypomelanotic skin status of individual homozygous SCD patient, if measured objectively by assessing the types and quantity of melanin in individual patient, influence the severity in phenotypic expression of SCD in affected patients. Oculocutaneous albinism (OCA) which is characterized by hypomelanosis is an inherited autosomal recessive disorder like SCD. OCA is also common in the tropics and sub-tropics like SCD. It had been reported that OCA does occur co-morbidly with homozygous SCD. Comparing a group of patients with co-morbid OCA and homozygous SCD with another group with SCD, who do not have OCA on severity of phenotypic expression of SCD could provide a feasible means of testing the hypothesis. If future carefully controlled studies confirm the hypothesis of influence of hypermelanotic or hypomelanotic skin status of the individual patients on severity in phenotypic expression of homozygous SCD, genetic and pharmacological interventions aimed at regulation of melanin production may play a role in alleviating the severity in phenotypic expression of SCD in affected patients.     

Painful sickle cell crises precipitated by stopping prophylactic exchange transfusions.

A patient with homozygous sickle cell disease showed a reduced incidence of painful crises as a result of regular exchange transfusion, but on three occasions when transfusion treatment was interrupted, a painful crisis occurred. Onset of painful crisis was associated with raised packed cell volume (PCV) or percentage of haemoglobin S (HbS%), or both. Measurement of whole blood viscosity using in vitro mixtures of blood group compatible normal (AA) and sickle (SS) cells showed that above an HbS of 25% any increase in PCV caused a disproportionate increase in whole blood viscosity. These clinical observations and laboratory data suggest that when regular exchange transfusions are terminated both HbS% and PCV should be carefully monitored. Prophylactic venesection should be considered for patients who maintain their PCV after transfusion as HbS% rises.     

Oxidative profile of sickle cell patients in a Cameroonian urban hospital

Background

Sickle cell disease (SCD) is a class of hemoglobinopathy resulting from a single mutation in the ß-globin chain inducing the substitution of valine for glutamic acid at the sixth amino acid position which leads to the production of abnormal haemoglobin (haemoglobin S [HbS]). Studies demonstrated the implication of oxidative stress in the development of the sickle cell disease.

Methods

The study aim was to determine the level of oxidative stress markers in a group of sickle cell homozygous patients (SS) in the Yaounde Central Hospital above 15 years of age. Hemolysates obtained from patients were used to investigate some oxidative stress markers including malondialdehyde (MDA), nitric oxide (NO), catalase (CAT), superoxide dismutase (SOD), peroxidase, total antioxidant capacity (TAC) and total protein concentration.

Results

Eighty four individuals, 42 males and 42 females participated (50 % each) with an age range of 15 to 55 years. The levels of markers were significantly higher in the healthy AA group than sickle (SS) (p?<?0.05), with the exception of MDA which was significantly high in sickle cell (SS) patients than healthy (p?=?0.037). With respect to the gender, both healthy and SS females showed a greater Total anti-oxidant capacity (65 μM) compared to the males (55 μM).

Conclusion

The increase in the oxidative stress level especially MDA in sickle cell homozygous patients compared to healthy AA individuals confirms that oxidative stress is involved in the pathogenesis of the sickle cell disease.